Chronic contact dermatitis is a major cause of disability in the workplace. Both irritant and allergic reactions are responsible for this morbidity. Once a worker is sensitized to a substance, little can be done to reduce or eliminate the allergy. Anecdotal information and a few studies suggest that some, but not many, workers become accommodated or "hardened" to the sensitizer. Mechanisms for the accommodation are not well worked out and some doubt the validity of the concept. We propose to study the mechanisms of specific and non-specific accommodation. We will use both humans and guinea pigs to study identical irritants and allergens. We will develop a validated animal model for the human accommodation response. We will identify a subset of individuals whose response to continued antigenic exposure is the acquisition of tolerance. The specificity of this state will be examined and its mechanism studied. In addition, special attention will be given to the role of Langerhans cells in accommodation. We will use an animal model to test Langerhans cell blockade as a mechanism of mimicking the accommodated state and blocking the elicitation of contact sensitivity.